Paclitaxel With or Without Bevacizumab in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

OBJECTIVES:

• Compare the time to treatment failure in patients with locally recurrent or metastatic breast cancer treated with paclitaxel with or without bevacizumab.
• Compare the objective response rate, duration of response, overall survival, and time to progression in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease-free interval (no more than 24 months vs more than 24 months), number of metastatic sites (less than 3 vs 3 or more), treatment with prior adjuvant chemotherapy (yes vs no), and estrogen receptor status (positive vs negative vs unknown). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 followed by bevacizumab IV over 30-90 minutes on days 1 and 15.
• Arm II: Patients receive paclitaxel as in arm I. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and on day 1 of weeks 17 and 33.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 316-650 patients (158-325 per treatment arm) will be accrued for this study within 31 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the breast
• Locally recurrent disease that is not amenable to surgical resection with curative intent OR
• Metastatic disease
• No HER-2-overexpressing (3+) breast cancer unless previously treated with trastuzumab (Herceptin)

• Unknown HER-2 status allowed provided herceptin-based therapy inappropriate or not indicated
• No prior or radiologic evidence of CNS metastases, including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No prior bleeding diathesis

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2 times upper limit of normal (ULN) (5 times ULN for known liver involvement)
• PT/PTT no greater than 1.5 times normal
• INR no greater than 1.5 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• No proteinuria by dipstick urinalysis
• Trace proteinuria allowed
• Proteinuria less than 500 mg by 24-hour urine collection if proteinuria at least 1+ by urinalysis

Cardiovascular:

• No clinically significant cardiovascular disease
• No myocardial infarction within the past 12 months
• No unstable angina
• No prior deep vein thrombosis
• No grade 2 or greater peripheral vascular disease
• No uncontrolled congestive heart failure
• No uncontrolled hypertension (systolic blood pressure greater than 170 mmHg and diastolic blood pressure greater than 95 mm Hg)
• No prior cerebrovascular accident

Pulmonary:

• No prior pulmonary embolism

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception
• No history of seizures
• No non-healing wound or fracture
• No hypersensitivity to paclitaxel, Cremophor EL, Chinese hamster ovary cell products, or other recombinant human antibodies
• No active infection requiring parenteral antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• No prior chemotherapy for locally recurrent or metastatic breast cancer
• At least 12 months since prior adjuvant or neoadjuvant taxane therapy
• At least 3 weeks since prior adjuvant chemotherapy

Endocrine therapy:

• At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic breast cancer

Radiotherapy:

• At least 3 weeks since prior radiotherapy
• No prior radiotherapy to only site of disease
• No concurrent local radiotherapy for pain control or life-threatening situations (e.g, superior vena cava syndrome, spinal cord compression, or CNS metastases)

Surgery:

• At least 4 weeks since prior major surgical procedure except placement of vascular access device or breast biopsy
• At least 7 days since prior minor surgical procedure, including placement of an access device or fine needle aspiration

Other:

• At least 10 days since prior anticoagulant therapy (low-dose anticoagulant therapy to maintain patency of a vascular access device allowed)
• At least 10 days since prior and no concurrent daily aspirin (more than 325 mg/day) or other non-steroidal anti-inflammatory medication known to inhibit platelet function
• No concurrent dipyridamole, ticlopidine, clopidogrel, or cilostazol